Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription

J Cell Mol Med. 2019 May;23(5):3345-3356. doi: 10.1111/jcmm.14225. Epub 2019 Mar 19.

Abstract

Objectives: This study focused on investigating the expression and underlying molecular mechanism of early growth response 1 (Egr1) in diabetic retinopathy.

Methods: A microarray assay was applied to examine differentially expressed genes in the retina tissues of normal rats, as well as in those of streptozotocin-induced diabetic rats. Human retinal vascular endothelial cells (HRVECs) transfected with sh-NC, sh-Egr1 or sh-Egr1+ pVax1-p53 were cultured under high-glucose conditions and then used to explore the role of Egr1 in vitro. The effect of Egr1 on retinal vascular dysfunction caused by diabetes was examined by sh-Egr1 administration in vivo RESULTS: Early growth response 1 was found to be up-regulated in the retinas of diabetic rats compared to those of normal rats. Down-regulation of Egr1 in HRVECs under high-glucose conditions inhibited the apoptosis, migration and tube formation in vitro. Moreover, sh-Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function by decreasing apoptotic cells and microvascular formation in vivo. The reduction of Egr1 evidently down-regulated the p53 expression. Overexpression of p53 rescued the inhibition of sh-Egr1 in HRVECs under high-glucose concentration on apoptosis, migration and tube formation in vitro.

Conclusion: Down-regulation of Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function via inhibiting p53 expression.

Keywords: Egr1; diabetic retinopathy; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Diabetes Mellitus, Experimental / physiopathology*
  • Early Growth Response Protein 1 / metabolism*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Glucose / toxicity
  • Humans
  • Male
  • Rats, Sprague-Dawley
  • Retinal Vessels / metabolism
  • Retinal Vessels / physiopathology*
  • Signal Transduction / drug effects
  • Transcription, Genetic*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Early Growth Response Protein 1
  • Tumor Suppressor Protein p53
  • Glucose